Compositions comprising combinations of organic acids

ABSTRACT

Provided are compositions comprising succinic acid, aconitic acid, and a carrier, wherein the succinic acid and aconitic acid are present in a ratio of from about 0.9:1 to about 40:1. Also provided are methods of disrupting a biofilm comprising applying to a surface having a biofilm a composition of the present invention.

FIELD OF THE INVENTION

The present invention relates to compositions comprising combinations oforganic acids and their uses. In certain embodiments, the presentinvention relates to compositions comprising combinations of succinicacid and aconitic acid and uses of such compositions for disruptingbiofilms.

BACKGROUND OF THE INVENTION

Organic acids, and combinations thereof, have been identified for use ina wide variety of compositions, including in compositions for oral care.For example, International Publication No. WO2012/001347 describes oralhealth compositions comprising extracts from shiitake mushroom, chicory,and/or raspberry, and low-molar mass fractions derived from theextracts. These compositions as described may comprise, or may besupplemented, with one or more of the following compounds: quinic acid,adenosine, inosine, trans-aconitic acid, cis-aconitic acid, oxalic acid,adenosine, and succinic acid. While the reference claims anti-biofilmeffects of its compositions via several mechanisms of action, it doesnot disclose any unexpected benefits resulting from any particularcombinations of the above compounds.

SUMMARY OF THE INVENTION

Applicants have discovered unexpectedly that certain combinations oforganic acids can be combined to make compositions that tend to exhibitsignificant and unexpected benefits, including increased biofilmdisruption.

According to certain embodiments, the present invention relates tocompositions comprising succinic acid, aconitic acid, and a carrier,wherein the succinic acid and aconitic acid are present in a ratio offrom about 0.9:1 to about 40:1.

According to certain other embodiments, the present invention relates tomethods of disrupting a biofilm comprising applying to a surface havinga biofilm a composition of the claimed invention.

According to certain other embodiments, the present invention relates tomethods of removing a biofilm from a surface comprising applying to asurface having a biofilm a composition of the claimed invention.

According to certain other embodiments, the present invention relates tomethods of reducing bacterial attachment to a surface comprisingapplying to the surface a composition of the claimed invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a plot of the percent removal of biofilm after multipletreatments (vs. water) versus percent reduction of bacterial attachment(vs. water) for formulations containing succinic acid (SA) and aconiticacid (AA) in varying ratios at a total concentration of 21 mM(0.25-0.37% w/w, depending on the ratio of SA to AA, see table 7).

FIG. 2 is a plot of the percent removal of biofilm after multipletreatments (vs. water) versus percent reduction of bacterial attachment(vs. water) for formulations containing succinic acid (SA) and aconiticacid (AA) in varying ratios (different from those in FIG. 1) at a totalconcentration of 21 mM (0.25-0.37% w/w, depending on the ratio of SA toAA, see table 7).

DETAILED DESCRIPTION OF THE INVENTION

All percentages listed in this specification are percentages ofsolids/active amounts by weight, unless otherwise specificallymentioned.

As noted above, applicants have discovered unexpectedly thatcompositions comprising combinations of both succinic acid and aconiticacid in a carrier tend to exhibit significant benefits over othercombinations of organic acids. In particular, in certain embodiments,applicants have discovered that such compositions exhibit significantincrease in disrupting biofilms. More specifically, as further describedherein below and shown in the Tables and Figures, applicants havediscovered that combinations of succinic acid and aconitic acid tend toexhibit significant increase in both (a) percent removal of biofilm and(b) percent reduction of bacterial attachment over other combinations oforganic acids. Applicants note that as used herein “disrupting abiofilm” refers to removal of biofilm from a surface, reduction ofbacterial attachment to a surface, or both.

Any suitable succinic acid may be used in the present invention.Succinic acid, also known by the IUPAC systematic name, butanedioicacid, or the historical name spirit of amber, is a diprotic,dicarboxylic acid with chemical formula C₄H₆O₄ and structural formulaHOOC—(CH₂)₂—COOH. The succinic acid used herein may be naturally orsynthetically derived. In certain embodiments, the succinic acid issynthetically derived. Commercially available sources of succinic acidinclude Acros Organics, Alfa Aesar, Fisher Chemical, Fluka, MPBiomedicals, Sigma Aldrich, Spectrum Chemicals, and TCI Fine Chemicals.

Any suitable aconitic acid may be used in the present invention.Aconitic acid, also known by the IUPAC systematic name,prop-1-ene-1,2,3-tricarboxylic acid, or the historical names Achilleicacid, Equisetic acid, Citridinic acid, or Pyrocitric acid, is an organicacid with chemical formula C₆H₆O₆ and structural formulaHO₂CCH═C(CO₂H)CH₂CO₂H, and having two isomers cis-aconitic acid andtrans-aconitic acid. In certain embodiments, the trans-aconitic acid isused. In other embodiments, the cis-aconitic acid is used. The aconiticacid used herein may be naturally or synthetically derived. In certainembodiments, the aconitic acid is synthetically derived. Commerciallyavailable sources of aconitic acid include Alfa Aesar, Fluka, MPBiomedicals, Parchem Fine & Specialty Chemicals, Sigma Aldrich, SpectrumChemicals, and TCI Fine Chemicals.

Any suitable amounts and ratios of the succinic acid and aconitic acidmay be used in the compositions of the present invention. As will berecognized by those of skill in the art, based on their respective pKavalues, the succinic and aconitic acids used in the present inventionwill be in equilibrium with their respective salt forms at most pHs.Accordingly, all amounts and ratios of succinic and aconitic aciddescribed and claimed herein refer to the total amount of such acid inboth its acid and salt form in a particular composition. For example, acomposition comprising 0.2% w/w of succinic acid has a total amount ofcombined solid/active succinic acid in its acid and salt forms of 0.2%w/w based on the total weight of the composition. A compositioncomprising a total combined amount of 1% w/w of succinic acid andtrans-aconitic acid comprises a combined solid/active amount of succinicacid in its acid and salt forms and trans-aconitic acid in its acid andsalt forms of 1% w/w based on the total weight of the compositions.

In certain embodiments, the succinic acid and aconitic acid are presentin the composition in a total combined amount that is effective toprevent and disrupt biofilm formation in the oral cavity and at whichthe composition is stable. Generally, the composition contains succinicacid and aconitic acid in a total combined amount of from about 0.1 toabout 2% by weight based on the total weight of the composition (% w/w).In certain embodiments, the total combined amount of succinic acid andaconitic acid is from about 0.1 to about 1% w/w of the composition, orfrom about 0.1 to about 0.9% w/w of the composition, or from about 0.1to about 0.5% w/w of the composition, or from about 0.1 to about 0.3%w/w of the composition. In certain embodiments, the compositioncomprises a total combined amount of succinic acid and aconitic acid offrom about 0.13% to about 0.89% w/w of the composition, from about 0.13%to about 0.52% w/w of the composition, or from about 0.13% to about 0.3%w/w of the composition.

Generally, the ratio of succinic acid to aconitic acid in thecompositions of the present invention (succinic:aconitic) is from about0.9:1 to about 40:1. In certain embodiments, the ratio of succinic acidto aconitic acid is from about 0.9:1 to about 20:1, or from about 0.9:1to about 14:1, or from about 0.9:1 to about 9:1, or from about 0.9:1 toabout 6:1, or from about 0.9:1 to about 4:1. In certain embodiments, theratio of succinic acid to aconitic acid is from about 1.1:1 to about20:1, or from about 2.5:1 to about 20:1, or from about 6:1 to about20:1, or from about 1.1:1 to about 14:1, or from about 2.5:1 to about14:1, or from about 6:1 to about 14:1, or from about 1.1:1 to about 9:1,or from about 2.5:1 to about 9:1, or from about 6:1 to about 9:1. Incertain embodiments, the ratio of succinic acid to aconitic acid is fromabout 1.3:1 to about 20:1, or from about 1.3:1 to about 13:1, or fromabout 1.3:1 to about 8.33:1, or from about 1.3:1 to about 6:1, or fromabout 2.5:1 to about 13:1, or from about 2.5:1 to about 8.33:1, or fromabout 2.5:1 to about 6:1, or from about 6:1 to about 8.33:1, or fromabout 4:1 to about 5.5:1. In certain preferred embodiments, the ratio ofsuccinic acid to aconitic acid from about 0.9:1 to about 14:1.

Any of a wide variety of orally-acceptable vehicles may be used in thepresent compositions. The vehicle can be aqueous or non-aqueous. Theaqueous vehicle is generally water, although water/alcohol mixtures mayalso be employed. In certain embodiments, water is added to q.s.(Quantum Sufficit, Latin for “as much as needed”) the composition. Incertain embodiments, the aqueous phase comprises from about 60% to about95%, or from about 75% to about 90%, by weight of the composition. Incertain compositions, water is present in an amount of from about 60% toabout 95%, or from about 75% to about 90%. Alternatively, thecompositions of the present invention may be formulated in a dry powder,chewing gum, film, semi-solid, solid or liquid concentrate form. In suchembodiments, for example, water is added to q.s. as necessary in thecase of liquid concentrates or powdered formulations, or water may beremoved using standard evaporation procedures known in the art toproduce a composition in dry powder form. Evaporated, or freeze driedforms are advantageous for storage and shipping.

In some embodiments, alcohol may be added to the composition. Any of avariety of alcohols represented by the formula R₃—OH, wherein R₃ is analkyl group having from 2 to 6 carbons, may be used in the presentinvention. Examples of suitable alcohols of formula R₃—OH includeethanol; n-propanol, iso-propanol; butanols; pentanols; hexanols, andcombinations of two or more thereof, and the like. In certainembodiments, the alcohol is, or comprises, ethanol.

In some embodiments, the alcohol may be present in the composition in anamount of about 10.0% v/v or greater of the total composition, or fromabout 10.0% to about 35.0% v/v of the total composition, or from about15.0% to about 30.0% v/v of the total composition and may be from about20.0% to about 25.0% v/v of the total composition.

In some embodiments, the compositions may comprise a reduced level ofalcohol. The phrase “reduced level” of alcohol means an amount of aR₃—OH alcohol of about 10% v/v or less, or about 5% v/v or less, orabout 1.0% v/v or less, or about 0.1% v/v or less by volume of the totalcomposition. In certain embodiments, the compositions of the presentinvention are free of R₃—OH alcohols.

The compositions of the present invention preferably have a pH of lessthan 7. In certain embodiments, the composition have a pH of from about3 to less than 7, or from about 3.5 to less than 7, or from about 3.5 toabout 6.5, or from about 3.5 to about 5.5, or from about 3.5 to about 5.

As will be recognized by those of skill in the art, the pH of thecomposition may be adjusted or achieved using a buffer in an amounteffective to provide the composition with a pH below 7. The compositioncan optionally comprise at least one pH modifying agents among thoseuseful herein include acidifying agents to lower pH, basifying agents toraise pH, and buffering agents to control pH within a desired range. Forexample, one or more compounds selected from acidifying, basifying andbuffering agents can be included to provide a pH of about 2 to about 7,or in various embodiments from about 3 to about 6, or from about 4 toabout 5. Any orally acceptable pH modifying agent can be used includingwithout limitation carboxylic and sulfonic acids, acid salts (e.g.,monosodium citrate, disodium citrate, monosodium malate, etc.), alkalimetal hydroxides such as sodium hydroxide, borates, silicates, imidazoleand mixtures thereof. One or more pH modifying agents are optionallypresent in a total amount effective to maintain the composition in anorally acceptable pH range. In certain embodiments, inorganic acids maybe used as the buffer added to the composition.

In certain embodiments, organic acids may be used as the buffer added tothe composition. Organic acids suitable for use in the compositions ofthe present invention include, but are not limited to, ascorbic acid,sorbic acid, citric acid, glycolic acid, lactic acid and acetic acid,benzoic acid, salicylic acid, phthalic acid, phenolsulphonic acid, andmixtures thereof, optionally, the organic acid is selected from thegroup consisting of benzoic acid, sorbic acid, citric acid and mixturesthereof, or optionally, the organic acid is benzoic acid.

Generally the amount of acidic buffer is between about 0.001% (or about0.001% w/v) to about 5.0% (or about 5.0% w/v) of the composition. Incertain embodiment, the organic acid buffer is present in amounts offrom 0.001% (or about 0.001% w/v) to 1.0% w/v (or about 1.0% w/v) of thecomposition, or between about 0.100% (or about 0.100% w/v) to about 1.0%(or about 1.0% w/v) of the composition.

The compositions of the present invention may further comprise any of avariety of optional ingredients therein, including, but not limited tooily components, active ingredients, additional surfactants, humectants,solvents, flavors, sweeteners, colorants, preservatives, pH adjusters,pH buffers, and the like.

Any of a variety of oily components may be used in the presentcompositions. The oily component may comprise any one or more oils, orother materials that are water insoluble, or substantiallywater-insoluble, meaning that its solubility is less than about 1% byweight in water at 25° C. or, optionally, less than about 0.1%. Incertain embodiments, the oily component of the present inventioncomprises, consists essentially of, or consists of, at least oneessential oil, i.e. a natural or synthetic (or combination thereof)concentrated hydrophobic material of vegetable origin, generallycontaining volatile compounds, at least one flavor oil, or a combinationof two or more thereof. Examples of suitable essential oils, flavoroils, and their amounts are described below. In certain embodiments, thecomposition comprises a total amount of oily component of about 0.05%w/w or more, about 0.1% w/w or more, or about 0.2% w/w or more of oilycomponent.

In certain embodiments, compositions of the present invention compriseessential oils. Essential oils are volatile aromatic oils which may besynthetic or may be derived from plants by distillation, expression orextraction, and which usually carry the odor or flavor of the plant fromwhich they are obtained. Useful essential oils may provide antisepticactivity. Some of these essential oils also act as flavoring agents.Useful essential oils include but are not limited to citra, thymol,menthol, methyl salicylate (wintergreen oil), eucalyptol, carvacrol,camphor, anethole, carvone, eugenol, isoeugenol, limonene, osimen,n-decyl alcohol, citronel, a-salpineol, methyl acetate, citronellylacetate, methyl eugenol, cineol, linalool, ethyl linalaol, safrolavanillin, spearmint oil, peppermint oil, lemon oil, orange oil, sageoil, rosemary oil, cinnamon oil, pimento oil, laurel oil, cedar leafoil, gerianol, verbenone, anise oil, bay oil, benzaldehyde, bergamotoil, bitter almond, chlorothymol, cinnamic aldehyde, citronella oil,clove oil, coal tar, eucalyptus oil, guaiacol, tropolone derivativessuch as hinokitiol, avender oil, mustard oil, phenol, phenyl salicylate,pine oil, pine needle oil, sassafras oil, spike lavender oil, storax,thyme oil, tolu balsam, terpentine oil, clove oil, and combinationsthereof.

In certain embodiments, the essential oils are selected from the groupconsisting of thymol ((CH₃)₂CHC₆H₃(CH₃)OH, also known asisopropyl-m-cresol), eucalyptol (C₁₀H₁₈O, also known as cineol), menthol(CH₃C₆H₉(C₃H₇)OH), also known as hexahydrothymol), methyl salicylate(C₆H₄OHCOOCH₃, also known as wintergreen oil), isomers of each of thesecompounds, and combinations of two or more thereof. In some embodiments,the compositions of the present invention contain thymol. In someembodiments, the compositions of the present invention contain menthol.In some embodiments, the composition contains all four of theseessential oils.

In certain embodiments, thymol is employed in amounts of from about0.0001% to about 0.6% w/v, or from about 0.005% to about 0.07% w/v ofthe composition. In certain embodiments, eucalyptol may be employed inamounts of from about 0.0001% to about 0.51 w/v, or from about 0.0085%to about 0.10% w/v of the composition. In certain embodiments, mentholis employed in amounts of from about 0.0001% to about 0.25% w/v, or fromabout 0.0035% to about 0.05% w/v of the composition. In certainembodiments, methyl salicylate is employed in amounts of from about0.0001% to about 0.28% w/v, or from about 0.004% to about 0.07% w/v ofthe composition. In certain embodiments, the total amount of all of suchessential oils present in the disclosed compositions can be from about0.0004% to about 1.64% w/v, or from about 0.0165% to about 0.49% w/v ofthe composition.

In certain embodiments, fluoride providing compounds may be present inthe mouth rinse compositions of this invention. These compounds may beslightly water soluble or may be fully water soluble and arecharacterized by their ability to release fluoride ions or fluoridecontaining ions in water. Typical fluoride providing compounds areinorganic fluoride salts such as soluble alkali metal, alkaline earthmetal, and heavy metal salts, for example, sodium fluoride, potassiumfluoride, ammonium fluoride, cupric fluoride, zinc fluoride, stannicfluoride, stannous fluoride, barium fluoride, sodium hexafluorosilicate,ammonium hexafluorosilicate, sodium fluorozirconate, sodiummonofluorophosphate, aluminum mono- and difluorophosphate andfluorinated sodium calcium pyrophosphate. Amine fluorides, such asN′-octadecyltrimethylendiamine-N,N,N′-tris(2-ethanol)-dihydrofluorideand 9-octadecenylamine-hydrofluoride), may also be used. In certainembodiments, the fluoride providing compound is generally present in anamount sufficient to release up to about 5%, or from about 0.001% toabout 2%, or from about 0.005% to about 1.5% fluoride by weight of thecomposition.

In certain embodiments, sensitivity reducing agents, such as potassiumsalts of nitrate and oxalate in an amount from about 0.1% to about 5.0%w/v of the composition may be incorporated into the present invention.Other potassium releasing compounds are feasible (e.g. KCl). Highconcentrations of calcium phosphates may also provide some addedsensitivity relief. These agents are believed to work by either formingan occlusive surface mineral deposit on the tooth surface or throughproviding potassium to the nerves within the teeth to depolarize thenerves. A more detailed discussion of suitable sensitivity reducingagents can be found in US 2006/0013778 to Hodosh and U.S. Pat. No.6,416,745 to Markowitz et al., both of which are herein incorporated byreference in their entirety.

In certain embodiments, compounds with anti-calculus benefits (e.g.various carboxylates, polyaspartic acid, etc.) may be incorporated intothe present invention. Also useful as an anticalculus agent are theanionic polymeric polycarboxylates. Such materials are well known in theart, being employed in the form of their free acids or partially orpreferably fully neutralized water soluble alkali metal (e.g. potassiumand preferably sodium) or ammonium salts. Preferred are 1:4 to 4:1 byweight copolymers of maleic anhydride or acid with another polymerizableethylenically unsaturated monomer, preferably methyl vinyl ether(methoxyethylene) having a molecular weight (M.W.) of about 30,000 toabout 1,000,000. These copolymers are available, for example, as Gantrez25 AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and preferably S-97Pharmaceutical Grade (M.W. 70,000), of GAF Chemicals Corporation.

Additional anti-calculus agents may be selected from the groupconsisting of polyphosphates (including pyrophosphates) and saltsthereof polyamino propane sulfonic acid (AMPS) and salts thereof;polyolefin sulfonates and salts thereof; polyvinyl phosphates and saltsthereof; polyolefin phosphates and salts thereof; diphosphonates andsalts thereof; phosphonoalkane carboxylic acid and salts thereof;polyphosphonates and salts thereof; polyvinyl phosphonates and saltsthereof; polyolefin phosphonates and salts thereof; polypeptides; andmixtures thereof; carboxy-substituted polymers; and mixtures thereof. Inone embodiment, the salts are alkali metal or ammonium salts.Polyphosphates are generally employed as their wholly or partiallyneutralized water-soluble alkali metal salts such as potassium, sodium,ammonium salts, and mixtures thereof. The inorganic polyphosphate saltsinclude alkali metal (e.g. sodium) tripolyphosphate, tetrapolyphosphate,dialkyl metal (e.g. disodium) diacid, trialkyl metal (e.g. trisodium)monoacid, potassium hydrogen phosphate, sodium hydrogen phosphate, andalkali metal (e.g. sodium) hexametaphosphate, and mixtures thereof.Polyphosphates larger than tetrapolyphosphate usually occur as amorphousglassy materials. In one embodiment the polyphosphates are thosemanufactured by FMC Corporation, which are commercially known asSodaphos (n≈6), Hexaphos (n≈13), and Glass H (n≈21, sodiumhexametaphosphate), and mixtures thereof. The pyrophosphate salts usefulin the present invention include, alkali metal pyrophosphates, di-,tri-, and monopotassium or sodium pyrophosphates, dialkali metalpyrophosphate salts, tetraalkali metal pyrophosphate salts, and mixturesthereof. In one embodiment the pyrophosphate salt is selected from thegroup consisting of trisodium pyrophosphate, disodium dihydrogenpyrophosphate (Na₂H₂P₂O₇), dipotassium pyrophosphate, tetrasodiumpyrophosphate (Na₄P₂O₇), tetrapotassium pyrophosphate (K₄P₂O₇), andmixtures thereof. Polyolefin sulfonates include those wherein the olefingroup contains 2 or more carbon atoms, and salts thereof. Polyolefinphosphonates include those wherein the olefin group contains 2 or morecarbon atoms. Polyvinylphosphonates include polyvinylphosphonic acid.Diphosphonates and salts thereof include azocycloalkane-2,2-diphosphonicacids and salts thereof, ions of azocycloalkane-2,2-diphosphonic acidsand salts thereof, azacyclohexane-2,2-diphosphonic acid,azacyclopentane-2,2-diphosphonic acid,N-methyl-azacyclopentane-2,3-diphosphonic acid, EHDP(ethane-1-hydroxy-1,1,-diphosphonic acid), AHP(azacycloheptane-2,2-diphosphonic acid),ethane-1-amino-1,1-diphosphonate, dichloromethane-diphosphonate, etc.Phosphonoalkane carboxylic acid or their alkali metal salts include PPTA(phosphonopropane tricarboxylic acid), PBTA(phosphonobutane-1,2,4-tricarboxylic acid), each as acid or alkali metalsalts. Polyolefin phosphates include those wherein the olefin groupcontains 2 or more carbon atoms. Polypeptides include polyaspartic andpolyglutamic acids.

In certain embodiments, zinc salts such as zinc chloride, zinc acetateor zinc citrate may be added as an astringent for an “antisepticcleaning” feeling, as a breath protection enhancer or as anti-calculusagent in an amount of from about 0.0025% w/v to about 0.75% w/v of thecomposition.

Any of a variety of additional surfactants may be used in the presentinvention. Suitable surfactants may include anionic, non-ionic,cationic, amphoteric, zwitterionic surfactants, and combinations of twoor more thereof. Examples of suitable surfactants are disclosed, forexample, in U.S. Pat. No. 7,417,020 to Fevola, et al which isincorporated in its entirety herein by reference.

In certain embodiments, the compositions of the present inventioncomprise a non-ionic surfactant. Those of skill in the art willrecognize that any of a variety of one or more non-ionic surfactantsinclude, but are not limited to, compounds produced by the condensationof alkylene oxide groups (hydrophilic in nature) with an organichydrophobic compound which may be aliphatic or alkyl-aromatic in nature.Examples of suitable nonionic surfactants include, but are not limitedto, alkyl polyglucosides; alkyl glucose amines, block copolymers such asethylene oxide and propylene oxide copolymers e.g. Poloxamers;ethoxylated hydrogenated castor oils available commercially for exampleunder the trade name CRODURET (Croda Inc., Edison, N.J.); alkylpolyethylene oxide e.g. Polysorbates, and/or; fatty alcohol ethoxylates;polyethylene oxide condensates of alkyl phenols; products derived fromthe condensation of ethylene oxide with the reaction product ofpropylene oxide and ethylene diamine; ethylene oxide condensates ofaliphatic alcohols; long chain tertiary amine oxides; long chaintertiary phosphine oxides; long chain dialkyl sulfoxides; and mixturesthereof.

Exemplary non-ionic surfactants are selected from the group known aspoly(oxyethylene)-poly(oxypropylene) block copolymers. Such copolymersare known commercially as poloxamers and are produced in a wide range ofstructures and molecular weights with varying contents of ethyleneoxide. These non-ionic poloxamers are non-toxic and acceptable as directfood additives. They are stable and readily dispersible in aqueoussystems and are compatible with a wide variety of formulations and otheringredients for oral preparations. These surfactants should have an HLB(Hydrophilic-Lipophilic Balance) of between about 10 and about 30 andpreferably between about 10 and about 25. By way of example, non-ionicsurfactants useful in this invention include the poloxamers identifiedas poloxamers 105, 108, 124, 184, 185, 188, 215, 217, 234, 235, 237,238, 284, 288, 333, 334, 335, 338, 407, and combinations of two or morethereof. In certain preferred embodiments, the composition comprisespoloxamer 407.

In certain embodiments, the compositions of the claimed inventioncomprise less than about 9% of non-ionic surfactant, less than 5%, orless than 1.5%, or less than 1%, or less than 0.8, less than 0.5%, lessthan 0.4%, or less than 0.3% of non-ionic surfactants. In certainembodiments, the composition of the present invention is free ofnon-ionic surfactants.

In certain embodiments, the compositions of the present invention alsocontain at least one alkyl sulfate surfactant. In certain embodiments,suitable alkyl sulfate surfactants include, but are not limited tosulfated C₈ to C₁₈, optionally sulfated C₁₀ to C₁₆ even numbered carbonchain length alcohols neutralized with a suitable basic salt such assodium carbonate or sodium hydroxide and mixtures thereof such that thealkyl sulfate surfactant has an even numbered C₈ to C₁₈, optionally C₁₀to C₁₆, chain length. In certain embodiments, the alkyl sulfate isselected from the group consisting of sodium lauryl sulfate, hexadecylsulfate and mixtures thereof. In certain embodiments, commerciallyavailable mixtures of alkyl sulfates are used. A typical percentagebreakdown of alkyl sulfates by alkyl chain length in commerciallyavailable sodium lauryl sulfate (SLS) is as follows:

Alkyl Component Chain Percentage Length in SLS C₁₂ >60% C₁₄ 20%-35% C₁₆<10% C₁₀  <1% C₁₈  <1%

In certain embodiments, the alkyl sulfate surfactant is present in thecomposition from about 0.001% to about 6.0% w/v, or optionally fromabout 0.1% to about 0.5% w/v of the composition.

Another suitable surfactant is one selected from the group consisting ofsarcosinate surfactants, isethionate surfactants and tauratesurfactants. Preferred for use herein are alkali metal or ammonium saltsof these surfactants, such as the sodium and potassium salts of thefollowing: lauroyl sarcosinate, myristoyl sarcosinate, palmitoylsarcosinate, stearoyl sarcosinate and oleoyl sarcosinate. Thesarcosinate surfactant may be present in the compositions of the presentinvention from about 0.1% to about 2.5%, or from about 0.5% to about 2%by weight of the total composition.

Zwitterionic synthetic surfactants useful in the present inventioninclude derivatives of aliphatic quaternary ammonium, phosphonium, andsulfonium compounds, in which the aliphatic radicals can be straightchain or branched, and wherein one of the aliphatic substituentscontains from about 8 to 18 carbon atoms and one contains an anionicwater-solubilizing group, e.g., carboxy, sulfonate, sulfate, phosphateor phosphonate.

The amphoteric surfactants useful in the present invention include, butare not limited to, derivatives of aliphatic secondary and tertiaryamines in which the aliphatic radical can be a straight chain orbranched and wherein one of the aliphatic substituents contains fromabout 8 to about 18 carbon atoms and one contains an anionicwater-solubilizing group, e.g., carboxylate, sulfonate, sulfate,phosphate, or phosphonate. Examples of suitable amphoteric surfactantsinclude, but are not limited alkylimino-diproprionates,alkylamphoglycinates (mono or di), alkylamphoproprionates (mono or di),alkylamphoacetates (mono or di), N-alkyl [3-aminoproprionic acids,alkylpolyamino carboxylates, phosphorylated imidazolines, alkylbetaines, alkylamido betaines, alkylamidopropyl betaines, alkylsultaines, alkylamido sultaines, and mixtures thereof. In certainembodiments, the amphoteric surfactant is selected from the groupconsisting of alkylamidopropyl betaines, amphoacetates such as sodiumauroamphoacetate and mixtures thereof. Mixtures of any of the abovementioned surfactants can also be employed. A more detailed discussionof anionic, nonionic and amphoteric surfactants can be found in U.S.Pat. No. 7,087,650 to Lennon; U.S. Pat. No. 7,084,104 to Martin et al.;U.S. Pat. No. 5,190,747 to Sekiguchi et al.; and U.S. Pat. No.4,051,234, Gieske, et al., each of which patents are herein incorporatedby reference in their entirety.

In certain embodiments, the compositions of the claimed inventioncomprise less than about 9% of amphoteric surfactant, less than 5%, orless than 1.5%, or less than 1%, or less than 0.8, less than 0.5%, lessthan 0.4%, or less than 0.3% of amphoteric surfactants. In certainembodiments, the composition of the present invention is free ofamphoteric surfactants.

Additional surfactants may be added with the alkyl sulfate surfactant toaid in solubilization of the essential oils provided such surfactants donot affect the bioavailability of the essential oils. Suitable examplesinclude additional anionic surfactants, nonionic surfactants, amphotericsurfactants and mixtures thereof. However, in certain embodiments, thetotal surfactant concentration (including the alkyl sulfate surfactantalone or in combination with other surfactants) for mouth rinses of thepresent invention should not exceed or should about 9% or less,optionally, the total surfactant concentration should be about 5% orless, optionally about 1% or less, optionally about 0.5% or less w/w %of active surfactant by weight of the composition.

In certain embodiments, a sugar alcohol (humectant) is also added to theoral compositions of the present invention. The sugar alcohol solvent(s)may be selected from those multi-hydroxy-functional compounds that areconventionally used in oral and ingestible products. In certainembodiments, the sugar alcohol (s) should be nonmetabolized andnon-fermentable sugar alcohol (s). In specific embodiments, the sugaralcohols include, but are not limited to sorbitol, glycerol, xylitol,mannitol, maltitol, inositol, allitol, altritol, dulcitol, galactitol,glucitol, hexitol, iditol, pentitol, ribitol, erythritol and mixturesthereof. Optionally, the sugar alcohol is selected from the groupconsisting of sorbitol and xylitol or mixtures thereof. In someembodiments, the sugar alcohol is sorbitol. In certain embodiments, thetotal amount of sugar alcohol (s), which are added to effectively aid inthe dispersion or dissolution of the mouth rinse or other ingredients,should not exceed about 50% w/ of the total composition. Or, totalamount of sugar alcohol should not exceed about 30% w/v of the totalcomposition. Or, total amount of sugar alcohol should not exceed 25% w/vof the total composition. The sugar alcohol can be in an amount of fromabout 1.0% to about 24% w/v, or from about 1.5% to about 22% w/v, orfrom about 2.5% to about 20% w/v of the total composition.

In certain embodiments, a polyol solvent is added to the composition.The polyol solvent comprises a polyol or polyhydric alcohol selectedfrom the group consisting of polyhydric alkanes (such as propyleneglycol, glycerin, butylene glycol, hexylene glycol, 1,3-propanediol);polyhydric alkane esters (dipropylene glycol, ethoxydiglycol);polyalkene glycols (such as polyethylene glycol, polypropylene glycol)and mixtures thereof. In certain embodiments, the polyol solvent can bepresent in an amount of from 0% to about 40% w/v, or from about 0.5% toabout 20% w/v, or from about 1.0% to about 10% w/v of the composition.

In certain embodiments, the compositions of the present invention have apH of about 11 or less. In some embodiments, the compositions have a pHof from about 3 to about 7, or from about 3.5 to about 6.5, or fromabout 3.5 to about 5.0.

As will be recognized by those of skill in the art, the pH of thecomposition may be adjusted or maintained using a buffer in an amounteffective to provide the composition with a pH at or below 11. Thecomposition can optionally comprise at least one pH modifying agentsamong those useful herein include acidifying agents to lower pH,basifying agents to raise pH, and buffering agents to maintain pH withina desired range. For example, one or more compounds selected fromacidifying, basifying and buffering agents can be included to provide apH of about 2 to about 7, or in various embodiments from about 3 toabout 6, or from about 4 to about 5. Any orally acceptable pH modifyingagent can be used including without limitation hydrochloric, carboxylicand sulfonic acids, acid salts (e.g., monosodium citrate, disodiumcitrate, monosodium malate, etc.), alkali metal hydroxides such assodium hydroxide, borates, silicates, imidazole and mixtures thereof.One or more pH modifying agents are optionally present in a total amounteffective to maintain the composition in an orally acceptable pH range.In certain embodiments, inorganic acids may be used as the buffer addedto the composition.

In certain embodiments, organic acids may be used as the buffer added tothe composition. Organic acids suitable for use in the compositions ofthe present invention include, but are not limited to, ascorbic acid,sorbic acid, citric acid, glycolic acid, lactic acid and acetic acid,benzoic acid, salicylic acid, phthalic acid, phenolsulphonic acid, andmixtures thereof, optionally, the organic acid is selected from thegroup consisting of benzoic acid, sorbic acid, citric acid and mixturesthereof, or optionally, the organic acid is benzoic acid.

Generally the amount of buffering compound is from about 0.001% to about20.0% of the composition. In certain embodiment, the organic acid bufferis present in amounts of from about 0.001% to about 10% w/v of thecomposition, or from about 0.01% to about 1% of the composition.

In certain embodiments, additional conventional components may be addedas in mouthwashes and mouth rinses of the prior art. Whereas somealcohol containing mouth rinses have a pH of about 7.0, reduction of thealcohol level may require the addition of acidic preservatives, such assorbic acid or benzoic acid, which reduce pH levels. Buffer systems arethen necessary to control the pH of the composition at optimal levels.This is generally accomplished through the addition of a weak acid andits salt or a weak base and its salt. In some embodiments, usefulsystems have been found to be sodium benzoate and benzoic acid inamounts of from 0.01% (or about 0.01% w/v) to 1.0% w/v (or about 1.0%w/v) of the composition, and sodium citrate and citric acid in amountsof from 0.001% (or about 0.001% w/v) to 1.0% w/v (or about 1.0% w/v) ofthe composition, phosphoric acid and sodium/potassium phosphate ofamounts from 0.01% (or about 0.01%) to 1.0% (or about 1.0%) by weight ofthe composition. In certain embodiments, the buffers are incorporated inamounts that maintain the pH at levels of from 3.0 (or about 3.0) to 8.0(or about 8.0), optionally from 3.5 (or about 3.5) to 6.5 (or about6.5), optionally from 3.5 (or about 3.5) to 5.0 (or about 5.0).

Additional buffering agents include alkali metal hydroxides, ammoniumhydroxide, organic ammonium compounds, carbonates, sesquicarbonates,borates, silicates, phosphates, imidazole, and mixtures thereof.Specific buffering agents include monosodium phosphate, trisodiumphosphate, sodium hydroxide, potassium hydroxide, alkali metal carbonatesalts, sodium carbonate, imidazole, pyrophosphate salts, sodiumgluconate, sodium lactate, citric acid, and sodium citrate.

Sweeteners such as aspartame, sodium saccharin (saccharin), sucralose,stevia, acesulfame K and the like may be added for better taste inamounts of from about 0.0001% w/v to about 1.0% w/v. In certainpreferred embodiments, the sweetener comprises sucralose.

In certain embodiments, the composition further comprises flavors orflavorants to modify or magnify the taste of the composition, or reduceor mask the sharp “bite” or “burn” of ingredients such as thymol.Suitable flavors include, but are not limited to, flavor oils such asoil of anise, anethole, benzyl alcohol, spearmint oil, citrus oils,vanillin and the like may be incorporated. Other flavors such as citrusoils, vanillin and the like may be incorporated to provide further tastevariations. In these embodiments, the amount of flavor oil added to thecomposition can be from about 0.001% to about 5% w/v, or from about0.01% to about 0.3% w/v of the total composition. The particular flavorsor flavorants, and other taste improving ingredients, employed will varydepending upon the particular taste and feel desired. Those skilled inthe art can select and customize these types of ingredients to providethe desired results.

In certain embodiments, acceptably approved food dyes may be used toprovide a pleasing color to the compositions of the invention. These maybe selected from, but not limited to, the long list of acceptable fooddyes. Suitable dyes for this purpose include FD&C yellow #5, FD&C yellow#10, FD&C blue #1 and FD&C green #3. These are added in conventionalamounts, typically in individual amounts of from about 0.00001% w/v toabout 0.0008% w/v, or from about 0.000035% w/v to about 0.0005% w/v ofthe composition.

Other conventional ingredients may be used in the liquid or mouth rinsecompositions of this invention, including those known and used in theart. Examples of such ingredients include thickeners, suspending agentsand softeners. Thickeners and suspending agents useful in thecompositions of the present invention can be found in U.S. Pat. No.5,328,682 to Pullen et al., herein incorporated by reference in itsentirety. In certain embodiments, these are incorporated in amounts offrom about 0.1% w/v to about 0.6% w/v, or about 0.5% w/v of thecomposition.

In some embodiments, antimicrobial preservatives may be added to thecomposition. Some antimicrobial preservatives which may be used include,but are not limited to cationic antibacterials, such as sodium benzoate,polyquaternium polycationic polymers (i.e polyquaternium-42:Poly[oxyethylene(dimethylimino)ethylene (dimethylimino)ethylenedichloride]), quaternary ammonium salts or quaternary ammoniumcompounds, parabens (i.e. parahydroxybenzoates or esters ofparahydroxybenzoic acid), hydroxyacetophenone, 1,2-Hexanediol, CaprylylGlycol, chlorhexidine, alexidine, hexetidine, benzalkonium chloride,domiphen bromide, cetylpyridinium chloride (CPC), tetradecylpyridiniumchloride (TPC), N-tetradecyl-4-ethylpyridinium chloride (TDEPC),octenidine, bisbiguanides, zinc or stannous ion agents, grapefruitextract, and mixtures thereof. Other antibacterial and antimicrobialagents include, but are not limited to:5-chloro-2-(2,4-dichlorophenoxy)-phenol, commonly referred to astriclosan; 8-hydroxyquinoline and its salts, copper II compounds,including, but not limited to, copper(II) chloride, copper(II) sulfate,copper(II) acetate, copper(II) fluoride and copper(II) hydroxide;phthalic acid and its salts including, but not limited to thosedisclosed in U.S. Pat. No. 4,994,262, including magnesium monopotassiumphthalate; sanguinarine; salicylanilide; iodine; sulfonamides;phenolics; delmopinol, octapinol, and other piperidino derivatives;niacin preparations; nystatin; apple extract; thyme oil; thymol;antibiotics such as augmentin, amoxicillin, tetracycline, doxycycline,minocycline, metronidazole, neomycin, kanamycin, cetylpyridiniumchloride, and clindamycin; analogs and salts of the above; methylsalicylate; hydrogen peroxide; metal salts of chlorite; pyrrolidoneethyl cocoyl arginate; lauroyl ethyl arginate monochlorohydrate; andmixtures of all of the above. In another embodiment, the compositioncomprises phenolic antimicrobial compounds and mixtures thereof.Antimicrobial components may be present from about 0.001% to about 20%by weight of the oral care composition. In another embodiment theantimicrobial agents generally comprise from about 0.1% to about 5% byweight of the oral care compositions of the present invention.

Other antibacterial agents may be basic amino acids and salts. Otherembodiments may comprise arginine.

In certain embodiments, the compositions may include whitening agents,oxidizing agents, anti-inflammatories, chelating agents, abrasives,combinations thereof, and the like.

A whitening agent may be included as an active in the presentcompositions. The actives suitable for whitening are selected from thegroup consisting of alkali metal and alkaline earth metal peroxides,metal chlorites, polyphosphates, perborates inclusive of mono andtetrahydrates, perphosphates, percarbonates, peroxyacids, andpersulfates, such as ammonium, potassium, sodium and lithiumpersulfates, and combinations thereof. Suitable peroxide compoundsinclude hydrogen peroxide, urea peroxide, calcium peroxide, carbamideperoxide, magnesium peroxide, zinc peroxide, strontium peroxide andmixtures thereof. In one embodiment the peroxide compound is carbamideperoxide. Suitable metal chlorites include calcium chlorite, bariumchlorite, magnesium chlorite, lithium chlorite, sodium chlorite, andpotassium chlorite. Additional whitening actives may be hypochlorite andchlorine dioxide. In one embodiment the chlorite is sodium chlorite. Inanother embodiment the percarbonate is sodium percarbonate. In oneembodiment the persulfates are oxones. The level of these substances isdependent on the available oxygen or chlorine, respectively, that themolecule is capable of providing to bleach the stain. In one embodimentthe whitening agents may be present at levels from about 0.01% to about40%, in another embodiment from about 0.1% to about 20%, in anotherembodiment form about 0.5% to about 10%, and in another embodiment fromabout 4% to about 7%, by weight of the oral care composition.

The compositions of the invention may contain an oxidizing agent, suchas a peroxide source. A peroxide source may comprise hydrogen peroxide,calcium peroxide, carbamide peroxide, or mixtures thereof. In someembodiments, the peroxide source is hydrogen peroxide. Other peroxideactives can include those that produce hydrogen peroxide when mixed withwater, such as percarbonates, e.g., sodium percarbonates. In certainembodiments, the peroxide source may be in the same phase as a stannousion source. In some embodiments, the composition comprises from about0.01% to about 20% of a peroxide source, in other embodiments from about0.1% to about 5%, in certain embodiments from about 0.2% to about 3%,and in another embodiment from about 0.3% to about 2.0% of a peroxidesource, by weight of the oral composition. The peroxide source may beprovided as free ions, salts, complexed, or encapsulated. It isdesirable that the peroxide in the composition is stable. The peroxidemay provide a reduction in staining, as measured by the Cycling StainTest, or other relevant methods.

Anti-inflammatory agents can also be present in the compositions of thepresent invention. Such agents may include, but are not limited to,non-steroidal anti-inflammatory (NSAID) agents oxicams, salicylates,propionic acids, acetic acids and fenamates. Such NSAIDs include but arenot limited to ketorolac, flurbiprofen, ibuprofen, naproxen,indomethacin, diclofenac, etodolac, indomethacin, sulindac, tolmetin,ketoprofen, fenoprofen, piroxicam, nabumetone, aspirin, diflunisal,meclofenamate, mefenamic acid, oxyphenbutazone, phenylbutazone andacetaminophen. Use of NSAIDs such as ketorolac are claimed in U.S. Pat.No. 5,626,838. Disclosed therein are methods of preventing and/ortreating primary and reoccurring squamous cell carcinoma of the oralcavity or oropharynx by topical administration to the oral cavity ororopharynx of an effective amount of an NSAID. Suitable steroidalanti-inflammatory agents include corticosteroids, such as fluccinolone,and hydrocortisone.

The present compositions may optionally contain chelating agents, alsocalled chelants or sequestrants, many of which also have anticalculusactivity or tooth substantive activity. Use of chelating agents in oralcare products is advantageous for their ability to complex calcium suchas found in the cell walls of bacteria. Chelating agents can alsodisrupt plaque by removing calcium from the calcium bridges which helphold this biomass intact. Chelating agents also have the ability tocomplex with metallic ions and thus aid in preventing their adverseeffects on the stability or appearance of products. Chelation of ions,such as iron or copper, helps retard oxidative deterioration of finishedproducts. In addition, chelants can in principle remove stains bybinding to teeth surfaces thereby displacing color bodies or chromagens.The retention of these chelants can also prevent stains from accruingdue to disruption of binding sites of color bodies on tooth surfaces.Therefore, chelants can aid in helping to mitigate stain and improvecleaning. A chelant may help to improve the cleaning as fused silica andabrasives clean in a mechanical mechanism while the chelant may help toprovide chemical cleaning Because the fused silica is a good mechanicalcleaner, there may be more stain removed so a chelant may be desired tohold, suspend, or complex with the stain so it is not able to restainthe tooth surface. Additionally, the chelant may coat the surface of thetooth to help prevent new stain. Chelants may be desired to be added toformulations containing cationic antibacterial agents. It may be desiredto add chelants to stannous containing formulations. The chelant is ableto help stabilize the stannous and keep a higher amount of the stannousbioavailable. The chelant may be used in stannous formulations whichhave a pH above about 4.0. In some formulations, the stannous may bestable without the need for a chelant as the stannous is more stablewith fused silica as compared to precipitated silica.

Suitable chelating agents include soluble phosphate compounds, such asphytates and linear polyphosphates having two or more phosphate groups,including tripolyphosphate, tetrapolyphosphate and hexametaphosphate,among others. Preferred polyphosphates are those having the number ofphosphate groups n averaging from about 6 to about 21, such as thosecommercially known as Sodaphos (n≈6), Hexaphos (n≈13), and Glass H(n≈21). Other polyphosphorylated compounds may be used in addition to orinstead of the polyphosphate, in particular polyphosphorylated inositolcompounds such as phytic acid, myo-inositol pentakis(dihydrogenphosphate); myo-inositol tetrakis(dihydrogen phosphate), myo-inositoltrikis(dihydrogen phosphate), and an alkali metal, alkaline earth metalor ammonium salt thereof. Preferred herein is phytic acid, also known asmyo-inositol 1,2,3,4,5,6-hexakis (dihydrogen phosphate) or inositolhexaphosphoric acid, and its alkali metal, alkaline earth metal orammonium salts. Herein, the term “phytate” includes phytic acid and itssalts as well as the other polyphosphorylated inositol compounds. Theamount of chelating agent in the compositions will depend on thechelating agent used and typically will be from at least about 0.1% toabout 20%, preferably from about 0.5% to about 10% and more preferablyfrom about 1.0% to about 7%.

Still other phosphate compounds that are useful herein for their abilityto bind, solubilize and transport calcium are the surface activeorganophosphate compounds described above useful as tooth substantiveagents including organic phosphate mono-, di- or triesters.

Other suitable agents with chelating properties for use in controllingplaque, calculus and stain include polyphosphonates described in U.S.Pat. No. 3,678,154 to Widder et al., U.S. Pat. No. 5,338,537 to White,Jr., and U.S. Pat. No. 5,451,401 to Zerby et al.; carbonyldiphosphonates in U.S. Pat. No. 3,737,533 to Francis; acrylic acidpolymer or copolymer in U.S. Pat. No. 4,847,070, Jul. 11, 1989 to Pyrzet al. and in U.S. Pat. No. 4,661,341, Apr. 28, 1987 to Benedict et al.;sodium alginate in U.S. Pat. No. 4,775,525, issued Oct. 4, 1988, toPera; polyvinyl pyrrolidone in GB 741,315, WO 99/12517 and U.S. Pat. No.5,538,714 to Pink et al.; and copolymers of vinyl pyrrolidone withcarboxylates in U.S. Pat. No. 5,670,138 to Venema et al. and in JPPublication No. 2000-063250 to Lion Corporation.

Still other chelating agents suitable for use in the present inventionare the anionic polymeric polycarboxylates. Such materials are wellknown in the art, being employed in the form of their free acids orpartially or preferably fully neutralized water soluble alkali metal(e.g. potassium and preferably sodium) or ammonium salts. Examples are1:4 to 4:1 copolymers of maleic anhydride or acid with anotherpolymerizable ethylenically unsaturated monomer, preferably methyl vinylether (methoxyethylene) having a molecular weight (M.W.) of about 30,000to about 1,000,000. These copolymers are available for example asGantrez® AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and S-97Pharmaceutical Grade (M.W. 70,000), of GAF Chemicals Corporation. Otheroperative polymeric polycarboxylates include the 1:1 copolymers ofmaleic anhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrrolidone, or ethylene, the latter being available forexample as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1:1copolymers of acrylic acid with methyl or hydroxyethyl methacrylate,methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.Additional operative polymeric polycarboxylates are disclosed in U.S.Pat. No. 4,138,477, Feb. 6, 1979 to Gaffar and U.S. Pat. No. 4,183,914,Jan. 15, 1980 to Gaffar et al. and include copolymers of maleicanhydride with styrene, isobutylene or ethyl vinyl ether; polyacrylic,polyitaconic and polymaleic acids; and sulfoacrylic oligomers of M.W. aslow as 1,000 available as Uniroyal ND-2. Other suitable chelants includepolycarboxylic acids and salts thereof described in U.S. Pat. No.5,015,467 to Smitherman U.S. Pat. Nos. 5,849,271 and 5,622,689 both toLukacovic; such as tartaric acid, citric acid, gluconic acid, malicacid; succinic acid, disuccinic acid and salts thereof, such as sodiumor potassium gluconate and citrate; citric acid/alkali metal citratecombination; disodium tartrate; dipotassium tartrate; sodium potassiumtartrate; sodium hydrogen tartrate; potassium hydrogen tartrate; acid orsalt form of sodium tartrate monosuccinate, potassium tartratedisuccinate, and mixtures thereof. In some embodiments, there may bemixtures or combinations of chelating agents.

Suitable abrasives for use in the present invention may include, but arenot limited to: perlite, silica such as sand or quartz, ground glass,silicon carbide, ilmenite (FeTiO₃), zircon oxide, zircon silicate,topaz, TiO₂, precipitated lime, chalk, flour of pumice, zeolites,talcum, kaolin, kieselguhr, aluminium oxide, silicates, zincorthophosphate, sodium bicarbonate (baking soda), plastic particles,alumina, hydrated alumina, calcium carbonate, calcium pyrophosphate, andmixtures thereof. The silica abrasive may be a natural amorphous silicaincluding diatomaceous earth; or a synthetic amorphous silica such as aprecipitated silica; or a silica gel, such as a silica xerogel; ormixtures thereof.

Generally, an amount of abrasive suitable for use in the composition ofthe invention will be empirically determined to provide an acceptablelevel of cleaning and polishing, in accordance with the techniques wellknown in the art. In one embodiment, a composition of the presentinvention includes an abrasive. In one embodiment, a compositionincludes a silica abrasive. In one embodiment, a silica abrasive ispresent in an amount of from 0.001 wt. % to 30 wt. %. In one embodiment,a silica abrasive is present in an amount of from 1 wt. % to 15 wt. %.In one embodiment, a silica abrasive is present in an amount of from 4wt. % to 10 wt. %

Other useful oral care actives and/or inactive ingredients and furtherexamples thereof can be found in U.S. Pat. No. 6,682,722 to Majeti etal. and U.S. Pat. No. 6,121,315 to Nair et al., each of which are hereinincorporated by reference in its entirety.

The compositions of the present invention may be made according to anyof a variety of methods disclosed herein and known in the art. Ingeneral, the described compositions may be prepared by combining thedesired components in a suitable container and mixing them under ambientconditions in any conventional mixing means well known in the art, suchas a mechanically stirred propeller, paddle, and the like.

The compounds and compositions of the present invention may be used in avariety of methods of treating a mammalian body, in particular fordisrupting a biofilm on a surface of the oral cavity. According tocertain embodiments, the present invention comprises disrupting biofilmon a surface by contacting the surface comprising biofilm with acomposition of the present invention. In certain embodiments, thepresent invention comprises removing biofilm from a surface bycontacting the surface comprising biofilm with a composition of thepresent invention. In certain embodiments, the present inventioncomprises reducing bacterial attachment to a surface by contacting thesurface with a composition of the present invention.

Any suitable surface of the oral cavity may be contacting in accord withthe methods of the present invention including one or more surfacesselected from the group consisting of surfaces of one or more teeth,surfaces of the gums, combinations of two or more thereof, and the like.

In each of the above methods, the composition of the claimed method maybe introduced to the surface to be contacted via any of a variety ofmethods. In certain embodiments, the composition is introduced into theoral cavity and applied to the surface by a user as a mouthwash or mouthrinse. In certain embodiments, the composition is introduced to the oralcavity and applied to the surface as a toothpaste on an article forcleaning the teeth, e.g. a toothbrush. The compositions of the presentinvention may be further introduced via the mouth and applied to thesurface as a gum, lozenge, dissolvable strip, or the like.

Furthermore, the contacting step of the methods of the present inventionmay comprise contacting the surface with the composition for anysuitable amount of time. In certain embodiments, the contacting stepcomprises contacting the surface for less than thirty seconds. Incertain embodiments, the contacting step comprises contacting thesurface with the composition for thirty seconds or more, for example,for about thirty seconds, for about 40 seconds, for about one minute, orfor greater than one minute.

EXAMPLES Example 1 Biofilm Prevention Performance of Compounds

Formulations A1-J1 as shown in Table 1 were made by dissolving one ofnine compounds: transcis-aconitic acid, succinic acid, adenosine, quinicacid, inosine, shikimic acid, uridine, oxalic acid, or epicatechin, inan aqueous solution containing ethanol and a benzoic acid buffer. Eachof the nine formulations were tested in a biofilm prevention assay asdescribed below.

The formulations were used to treat pellicle-coated hydroxyapatite peglids by immersing the lids in the formulations as treatment solutions.The peg lids were then removed from the treatment solutions andinoculated overnight with human whole saliva, in order to generate amixed species saliva-derived biofilm. The amount of biofilm grown oneach peg lid was quantified by measuring ATP using a bioluminescencereaction, and compared to the amount of biofilm grown on a peg lidexposed to the benzoic acid/ethanol solution negative control (sampleJ). The results are reported as log RLU, with a lower valuecorresponding to less biofilm. The resulting Log RLUs are reported inTable 1.

TABLE 1 Formulations of nine components. Raw Material (w/w %) A1 B1 C1D1 E1 F1 G1 H1 I1 J1 cis-Aconitic 0.5 — — — — — — — — — acid Succinicacid — 0.5 — — — — — — — — Adenosine — — 0.5 — — — — — — — Quinic acid —— — 0.5 — — — — — — Inosine — — — — 0.5 — — — — — Shikimic acid — — — —— 0.5 — — — — Uridine — — — — — — 0.5 — — — Oxalic acid — — — — — — —0.5 — — Epicatechin — — — — — — — — 0.5 — Benzoic acid 0.15 0.15 0.150.15 0.15 0.15 0.15 0.15 0.15 0.15 Ethanol 17.94 17.94 17.94 17.94 17.9417.94 17.94 17.94 17.94 17.94 Water 81.4 81.4 81.4 81.4 81.4 81.4 81.481.4 81.4 81.4 TOTAL 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0100.0 100.0 log RLU 5.90 5.94 6.17 6.17 6.17 6.20 6.23 6.37 6.68 6.30log SD 0.11 0.11 0.14 0.10 0.14 0.05 0.13 0.07 0.08 0.08

Example 2 Exploration of Different Ratios and Concentration Ranges forSuccinic Acid/Trans-Aconitic Acid

Succinic acid and trans-aconitic acid were formulated into full mouthrinse formulations and their concentrations and ratios weresystematically varied. The amounts and materials of each formulation isshown on Tables 2 through 5. Formulations containing succinic acid,trans-aconitic acid, and blends of both succinic acid and trans-aconiticacid were made. The total concentration of succinic acid plustrans-aconitic acid used in the formulations shown on Tables 3 through 6are 10.5 mM, 21 mM, 42 mM, and 63 mM, i.e. between 0.12% w/w and 1.1%w/w, respectively. These formulations were prepared by dissolving watersoluble components, including succinic acid, trans-aconitic acid,Poloxamer 407, sodium lauryl sulfate, sodium benzoate, saccharin,sucralose, sorbitol, and FD&C Green#3, in water. Separately, allnon-water soluble components, including menthol, thymol, eucalyptol,methyl salicylate, flavor, and benzoic acid, were dissolved in propyleneglycol. The propylene glycol solution was then added to the aqueoussolution and mixed.

TABLE 2 Formulations to find synergies of succinic acid (SA) andt-aconitic acid (tAA) mixtures. Total concentration of SA and tAA was10.5 mM, 0.12-0.18% by weight or 0.15% +/− 0.03% Raw material (w/w %)A10.5 B10.5 C10.5 D10.5 E10.5 F10.5 G10.5 H10.5 I10.5 Succinic Acid0.071 0.088 0.11 0.11 0.12 0.12 0.12 0.12 — Aconitic Acid 0.078 0.0520.026 0.020 0.013 0.0087 0.0044 — 0.18 Menthol 0.019 0.019 0.019 0.0190.019 0.019 0.019 0.019 0.019 Thymol 0.031 0.031 0.031 0.031 0.031 0.0310.031 0.031 0.031 Methyl Salicylate 0.032 0.032 0.032 0.032 0.032 0.0320.032 0.032 0.032 Eucalyptol 0.045 0.045 0.045 0.045 0.045 0.045 0.0450.045 0.045 Poloxamer 407 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10Sodium Lauryl 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 SulfateBenzoic Acid 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 SodiumBenzoate 0.11 0.11 0.11 0.11 0.11 0.11 0.11 0.11 0.11 Saccharin 0.0610.061 0.061 0.061 0.061 0.061 0.061 0.061 0.061 Sucralose 0.010 0.0100.010 0.010 0.010 0.010 0.010 0.010 0.010 Propylene Glycol 7.0 7.0 7.07.0 7.0 7.0 7.0 7.0 7.0 Sorbitol 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.010.0 FD&C Green #3 0.000037 0.000037 0.000037 0.000037 0.000037 0.0000370.000037 0.000037 0.000037 Flavor 0.017 0.017 0.017 0.017 0.017 0.0170.017 0.017 0.017 Water 82.3 82.3 82.3 82.3 82.3 82.3 82.3 82.2 82.4TOTAL 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 [SA]/[tAA]ratio 0.9:1 1.7:1 4.2:1 5.5:1 9.2:1 13.8:1 27.3:1 — —

TABLE 3 Formulations to find synergies of succinic acid (SA) andt-aconitic acid (tAA) mixtures. Total concentration of SA and tAA was 21mM, 0.25%-0.37% w/w Raw material A21 B21 C21 D21 E21 F21 Succinic 0.0350.071 0.11 0.14 0.18 0.21 Acid trans- 0.31 0.26 0.21 0.16 0.10 0.052Aconitic Acid Menthol 0.019 0.019 0.019 0.019 0.019 0.019 Thymol 0.0310.031 0.031 0.031 0.031 0.031 Methyl 0.032 0.032 0.032 0.032 0.032 0.032Salicylate Eucalyptol 0.045 0.045 0.045 0.045 0.045 0.045 Poloxamer 0.100.10 0.10 0.10 0.10 0.10 407 Sodium 0.10 0.10 0.10 0.10 0.10 0.10 LaurylSulfate Benzoic 0.05 0.05 0.05 0.05 0.05 0.05 Acid Sodium 0.11 0.11 0.110.11 0.11 0.11 Benzoate Saccharin 0.061 0.061 0.061 0.061 0.061 0.061Sucralose 0.010 0.010 0.010 0.010 0.010 0.010 Propylene 7.0 7.0 7.0 7.07.0 7.0 Glycol Sorbitol 10.0 10.0 10.0 10.0 10.0 10.0 FD&C 0.0000370.000037 0.000037 0.000037 0.000037 0.000037 Green #3 Flavor 0.017 0.0170.017 0.017 0.017 0.017 Water 82.1 82.1 82.1 82.1 82.1 82.2 TOTAL 100.0100.0 100.0 100.0 100.0 100.0 [SA]/[tAA] 0.1:1 0.3:1 0.5:1 0.9:1 1.8:14:1 Raw material G21 H21 I21 J21 K21 L21 Succinic 0.22 0.23 0.24 0.240.25 — Acid trans- 0.039 0.026 0.017 0.0087 — 0.37 Aconitic Acid Menthol0.019 0.019 0.019 0.019 0.019 0.019 Thymol 0.031 0.031 0.031 0.031 0.0310.031 Methyl 0.032 0.032 0.032 0.032 0.032 0.032 Salicylate Eucalyptol0.045 0.045 0.045 0.045 0.045 0.045 Poloxamer 0.10 0.10 0.10 0.10 0.100.10 407 Sodium 0.10 0.10 0.10 0.10 0.10 0.10 Lauryl Sulfate Benzoic0.05 0.05 0.05 0.05 0.05 0.05 Acid Sodium 0.11 0.11 0.11 0.11 0.11 0.11Benzoate Saccharin 0.061 0.061 0.061 0.061 0.061 0.061 Sucralose 0.0100.010 0.010 0.010 0.010 0.010 Propylene 7.0 7.0 7.0 7.0 7.0 7.0 GlycolSorbitol 10.0 10.0 10.0 10.0 10.0 10.0 FD&C 0.000037 0.000037 0.0000370.000037 0.000037 0.000037 Green #3 Flavor 0.017 0.017 0.017 0.017 0.0170.017 Water 82.2 82.2 82.2 82.2 82.2 82.0 TOTAL 100.0 100.0 100.0 100.0100.0 100.0 [SA]/[tAA] 5.6:1 8.8:1 14.1:1 27.6:1 — —

TABLE 4 Formulations to find synergies of succinic acid (SA) andt-aconitic acid (tAA) mixtures. Total concentration of SA and tAA was 42mM, 0.50-0.73% w/w Raw material A42 B42 C42 D42 E42 F42 G42 H42 I42Succinic Acid 0.28 0.35 0.42 0.44 0.46 0.47 0.48 0.5 — trans-aconiticAcid 0.31 0.21 0.10 0.078 0.052 0.035 0.017 — 0.73 Menthol 0.019 0.0190.019 0.019 0.019 0.019 0.019 0.019 0.019 Thymol 0.031 0.031 0.031 0.0310.031 0.031 0.031 0.031 0.031 Methyl Salicylate 0.032 0.032 0.032 0.0320.032 0.032 0.032 0.032 0.032 Eucalyptol 0.045 0.045 0.045 0.045 0.0450.045 0.045 0.045 0.045 Poloxamer 407 0.10 0.10 0.10 0.10 0.10 0.10 0.100.10 0.10 Sodium Lauryl 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10Sulfate Benzoic Acid 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 SodiumBenzoate 0.11 0.11 0.11 0.11 0.11 0.11 0.11 0.11 0.11 Saccharin 0.0610.061 0.061 0.061 0.061 0.061 0.061 0.061 0.061 Sucralose 0.010 0.0100.010 0.010 0.010 0.010 0.010 0.010 0.010 Propylene Glycol 7.0 7.0 7.07.0 7.0 7.0 7.0 7.0 7.0 Sorbitol 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.010.0 FD&C Green #3 0.000037 0.000037 0.000037 0.000037 0.000037 0.0000370.000037 0.000037 0.000037 Flavor 0.017 0.017 0.017 0.017 0.017 0.0170.017 0.017 0.017 Water 81.8 81.9 81.9 81.9 81.9 81.9 81.9 81.9 81.7TOTAL 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 [SA]/[tAA]0.9:1 1.7:1 4.2:1 5.6:1 8.8:1 13.4:1 28.2:1 — —

TABLE 5 Formulations to find synergies of succinic acid (SA) andt-aconitic acid (tAA) mixtures. Total concentration of SA and tAA was 63mM, 0.74-1.10% w/w Raw material A63 B63 C63 D63 E63 F63 G63 H63 I63Succinic Acid 0.42 0.53 0.64 0.66 0.69 0.71 0.73 0.74 — Aconitic Acid0.47 0.31 0.16 0.12 0.078 0.052 0.026 — 1.10 Menthol 0.019 0.019 0.0190.019 0.019 0.019 0.019 0.019 0.019 Thymol 0.031 0.031 0.031 0.031 0.0310.031 0.031 0.031 0.031 Methyl Salicylate 0.032 0.032 0.032 0.032 0.0320.032 0.032 0.032 0.032 Eucalyptol 0.045 0.045 0.045 0.045 0.045 0.0450.045 0.045 0.045 Poloxamer 407 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.100.10 Sodium Lauryl 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 SulfateBenzoic Acid 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 SodiumBenzoate 0.11 0.11 0.11 0.11 0.11 0.11 0.11 0.11 0.11 Saccharin 0.0610.061 0.061 0.061 0.061 0.061 0.061 0.061 0.061 Sucralose 0.010 0.0100.010 0.010 0.010 0.010 0.010 0.010 0.010 Propylene Glycol 7.0 7.0 7.07.0 7.0 7.0 7.0 7.0 7.0 Sorbitol 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.010.0 FD&C Green #3 0.000037 0.000037 0.000037 0.000037 0.000037 0.0000370.000037 0.000037 0.000037 Flavor 0.017 0.017 0.017 0.017 0.017 0.0170.017 0.017 0.017 Water 81.5 81.6 81.6 81.6 81.6 81.7 81.7 81.7 81.3TOTAL 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 [SA]/[tAA]0.9:1 1.7:1 4.0:1 5.5:1 8.8:1 13.7:1 28.1:1 — —

Two methods were used to test the effectiveness of the formulations. Thefirst was a “Multi-Treatment Static Biofilm with Pretreatment AssayMethod”, while the second was a “Prevention Assay Method”. The testmethods are described below.

Multi Treatment Static Biofilm with Pretreatment Assay Method

The formulations were prepared as described above using conventionalmixing technology. The pH of the formulations were all about pH 4.2. Apolystyrene peg plate (96 pegs, N=8 per group) were exposed to salivafor thirty minutes to form a pellicle on each peg at a temperature of35° C. Then, for each formulation, eight pegs (N=8) were pre-treated forten minutes with the formulation using an orbital shaker set to 500 RPMat room temperature. As a negative control, eight pegs (N=8) werepre-treated for ten minutes with sterile water. Next, a 24-hour salivarybiofilm was grown on these polystyrene peg plates at a temperature of35° C. The pegs were then re-treated (N=8) for thirty seconds with thesame formulation used for pre-treatment using an orbital shaker set to500 RPM at room temperature. The re-treatments were applied twice dailyfor two days, a total of six treatments including the pre-treatment.

After all treatments were complete, the biofilm from each peg wasneutralized and rinsed. The biofilm was harvested via sonication using aQ-Sonica Q700 Ultrasonic Liquid Processor with 431MP4-00 microplate hornDamper and 0.5:1 reverse gain booster (Q-Sonica, Newtown, Conn.). Usinga Celsis Rapid Detection RapiScreen kit (Celsis International PLC,Chicago, Ill.), the bacteria were lysed with Celsis Luminex and then theadenosine triphosphate (ATP) from the lysed bacteria was measured usingthe bioluminescence marker Celcis Luminate and a Centro LB 960Microplate Luminometer supplied by Berthold Technologies (Wildbad,Germany). Data were reported in log RLU (relative light units) wheredecreasing log RLUs indicated fewer viable bacteria remained on thebiofilm substrate.

Prevention Assay Method

The formulations were prepared as described above using conventionalmixing technology. The pH of the formulations were all about pH 4.2. Ahydroxyapatite-coated polystyrene peg plate (96 pegs, N=8 per group) wasexposed to saliva for one minute to form a pellicle at a temperature of35 C. Then, for each formulation, eight pegs (N=8) were pre-treated forten minutes with the formulation using an orbital shaker set to 500 RPMat room temperature. As a negative control, eight pegs (N=8) werepre-treated for ten minutes with sterile water. Next, a 16-hour salivarybiofilm was grown on these polystyrene peg plates at a temperature of 35C.

After all treatments were complete, the biofilm from each peg wasneutralized and rinsed. The biofilm was harvested via sonication using aQ-Sonica Q700 Ultrasonic Liquid Processor with 431MP4-00 microplate hornDamper and 0.5:1 reverse gain booster (Q-Sonica, Newtown, Conn.). Usinga Celsis Rapid Detection RapiScreen kit (Celsis International PLC,Chicago, Ill.), the bacteria were lysed with Celsis Luminex and then theadenosine triphosphate (ATP) from the lysed bacteria was measured usingthe bioluminescence marker Celcis Luminate and a Centro LB 960Microplate Luminometer supplied by Berthold Technologies (Wildbad,Germany). Data were reported in log RLU (relative light units) wheredecreasing log RLUs indicated fewer viable bacteria remained on thebiofilm substrate.

The results of the “Multi-Treatment Static Biofilm with PretreatmentAssay Method”, and the “Prevention Assay Method” for each of theformulations are summarized in Table 6.

FIGS. 1 and 2 are plots of the percent removal of biofilm after multipletreatments (vs. water) versus percent reduction of bacterial attachment(vs. water) for formulations A21-L21 containing succinic acid (SA) andtrans-aconitic acid (tAA) shown in Table 3 above. The dotted lines onthe figures are the straight line expected results of the blends of SAand tAA. The figures show that when succinic acid and trans-aconiticacid are combined in ratios between 0.9:1 and 14.1:1 (Succinicacid:trans-aconitic acid), the results deviate surprisingly from theexpected results.

Table 6 shows the same surprising results when examining the distancefrom the expected results for blends of succinic acid and trans-aconiticacid for other concentrations of the combined acid materials in theTable.

TABLE 6 Summarized results for Multi-Treatment and Prevention tests forformulations containing succinic acid (SA) and trans-aconitic acid(tAA). Predicted additive reduction Actual in % biofilm reduction ofReduction reduction total biofilm Biofilm of (prevention + (prevention +removal Reduction bacterial multi- multi- (% reduced of attachmenttreatment)* treatment)** Biofilm over bacterial (% reduced comparedcompared to SA + tAA removal water attachment over water to water waterFormula wt % [SA]/[tAA] (logRLU) control) (logRLU) control) controlcontrol Experiment 1 I10.5 0.18   0:1 4.66 35.72 6.00 6.40 42.12 42.12A10.5 0.15 0.9:1 4.53 37.52 5.86 8.58 43.11 46.1 B10.5 0.14 1.7:1 4.4239.03 5.79 9.67 43.44 48.7 C10.5 0.14 4.2:1 4.46 38.48 5.61 12.48 43.8250.96 H10.5 0.12   1:0 5.13 29.24 5.45 14.98 44.22 44.22 water 0.00 —7.25 0.00 6.41 0.00 0.00 0.00 Experiment 2 I10.5 0.18   0:1 5.13 29.925.81 9.36 39.28 39.28 D10.5 0.13 5.5:1 4.48 38.80 5.63 12.17 41.75 50.97E10.5 0.13 9.2:1 4.83 34.02 5.47 14.66 41.95 48.68 F10.5 0.13 13.8:1 5.06 30.87 5.5 14.20 42.04 45.07 G10.5 0.12 27.3:1  5.44 25.68 5.4814.51 42.14 40.19 H10.5 0.12   1:0 5.37 26.64 5.41 15.60 42.24 42.24water 0.00 — 7.32 0.00 6.41 0.00 0.00 0 Experiment 3 L21 0.37   0:1 4.6139.10 5.67 14.22 53.32 53.32 A21 0.35 0.1:1 4.6 39.23 5.65 14.52 53.3253.75 B21 0.33 0.3:1 4.92 35.01 5.58 15.58 53.32 50.59 C21 0.32 0.5:14.81 36.46 5.5 16.79 53.31 53.25 D21 0.30 0.9:1 4.42 41.61 5.29 19.9753.32 61.58 E21 0.28 1.8:1 4.14 45.31 5.26 20.42 53.31 65.73 F21 0.264.0:1 4.65 38.57 5.2 21.33 53.30 59.9 K21 0.25   1:0 5.23 30.91 5.1322.39 53.30 53.3 water 0.00 — 7.57 0.00 6.61 0.00 0.00 0 Experiment 4L21 0.37   0:1 5.1 30.33 5.82 7.77 38.10 38.1 G21 0.26 5.6:1 4.29 41.395.48 13.15 41.31 54.54 H21 0.26 8.8:1 4.69 35.93 5.47 13.31 41.49 49.24I21 0.26 14.1:1  5.05 31.01 5.44 13.79 41.63 44.8 J21 0.25 27.6:1  5.2927.73 5.43 13.95 41.75 41.68 K21 0.25   1:0 5.31 27.46 5.4 14.42 41.8841.88 water 0.00 — 7.32 0.00 6.31 0.00 0.00 0 Experiment 5 I42 0.73  0:1 4.77 34.21 5.82 9.20 43.41 43.41 A42 0.59 0.9:1 4.51 37.79 5.7310.61 47.53 48.4 B42 0.56 1.7:1 4.34 40.14 5.66 11.70 48.88 51.84 C420.52 4.2:1 4.41 39.17 5.41 15.60 50.43 54.77 H42 0.50   1:0 4.66 35.725.36 16.38 52.10 52.1 water 0.00 — 7.25 0.00 6.41 0.00 0.00 0 Experiment6 I42 0.73   0:1 5.05 31.01 5.73 10.61 41.62 41.62 D42 0.52 5.6:1 4.1443.44 5.38 16.07 46.23 59.51 E42 0.51 8.8:1 4.53 38.11 5.41 15.60 46.5053.71 F42 0.51 13.4:1  5 31.69 5.3 17.32 41.62 49.01 G42 0.50 28.2:1 5.11 30.19 5.31 17.16 46.86 47.35 H42 0.50   1:0 5.12 30.05 5.32 17.0047.05 47.05 water 0.00 — 7.32 0.00 6.41 0.00 0.00 0 Experiment 7 I631.10   0:1 5.48 25.85 5.86 12.14 37.99 37.99 A63 0.89 0.9:1 4.08 44.795.69 14.69 37.99 59.48 B63 0.84 1.7:1 3.97 46.28 5.69 14.69 42.23 60.97C63 0.80 4.0:1 4.03 45.47 5.65 15.29 43.38 60.76 D63 0.78 5.5:1 4.2642.35 5.55 16.79 43.69 59.14 E63 0.77 8.8:1 4.62 37.48 5.5 17.54 44.0455.02 F63 0.76 13.7:1  5.24 29.09 5.41 18.89 44.27 47.98 G63 0.7628.1:1  5.11 30.85 5.39 19.19 37.99 50.04 H63 0.74   1:0 5.58 24.49 5.3220.24 44.73 44.73 water 0.00 — 7.39 0.00 6.67 0.00 0.00 0

Example 3 Biofilm Prevention Performance of Compounds

Formulations A2-J2 as shown in Table 7 were made and tested in thebiofilm prevention assay. The formulations were tested in an in-vitrostatic multi-treatment mixed species biofilm assay. Pellicle-coated peglids were pre-treated with each formulation before biofilm growth. Thetreated peg lids were then inoculated with human whole saliva for 24hours in order to grow a mixed species saliva-derived biofilm. Thisbiofilm was treated with each formulation twice a day over the course of60 hours, for a total of five 30-second treatments. The results arereported as log RLU and are shown in Table 7, with a lower valuecorresponding to less biofilm. The results were then used to createcontour surfaces to maximize activity with varying concentrations ofsuccinic acid and trans-aconitic acid. A positive control (Sample J2)comprised of a standard essential oil containing mouth rinse was alsoformulated and tested.

TABLE 7 Formulations to find synergies of SAA and tAA mixtures. Rawmaterial A2 B2 C2 D2 E2 Succinic Acid 0.21 0.21 0.25 0.12 0.037 AconiticAcid 0.037 0.021 0.12 0.12 0.037 Menthol 0.038 0.038 0.038 0.038 0.038Thymol 0.062 0.062 0.062 0.062 0.062 Methyl Salicylate 0.064 0.064 0.0640.064 0.064 Eucalyptol 0.090 0.090 0.090 0.090 0.090 Poloxamer 407 0.200.20 0.20 0.20 0.20 Sodium Lauryl 0.20 0.20 0.20 0.20 0.20 SulfateBenzoic Acid 0.086 0.086 0.086 0.086 0.086 Sodium 0.077 0.077 0.0770.077 0.077 Benzoate Saccharin 0.061 0.061 0.061 0.061 0.061 Sucralose0.010 0.010 0.010 0.010 0.010 Propylene Glycol 7.0 7.0 7.0 7.0 7.0Sorbitol 10.0 10.0 10.0 10.0 10.0 FD&C Green #3 0.000037 0.0000370.000037 0.000037 0.000037 Flavor 0.017 0.017 0.017 0.017 0.017 Water81.8 81.7 81.7 81.8 82.0 TOTAL 100.0 100.0 100.0 100.0 100.0 log RLU3.80 3.92 3.97 3.99 4.01 Raw material F2 G2 H2 I2 J2 Succinic Acid 0.12— 0.037 0.12 — Aconitic Acid — 0.12 0.21 0.25 — Menthol 0.038 0.0380.038 0.038 0.038 Thymol 0.062 0.062 0.062 0.062 0.062 Methyl Salicylate0.064 0.064 0.064 0.064 0.064 Eucalyptol 0.090 0.090 0.090 0.090 0.090Poloxamer 407 0.20 0.20 0.20 0.20 0.20 Sodium Lauryl 0.20 0.20 0.20 0.200.20 Sulfate Benzoic Acid 0.086 0.086 0.086 0.086 0.086 Sodium 0.0770.077 0.077 0.077 0.077 Benzoate Saccharin 0.061 0.061 0.061 0.061 0.061Sucralose 0.010 0.010 0.010 0.010 0.010 Propylene Glycol 7.0 7.0 7.0 7.07.0 Sorbitol 10.0 10.0 10.0 10.0 10.0 FD&C Green #3 0.000037 0.0000370.000037 0.000037 0.000037 Flavor 0.017 0.017 0.017 0.017 0.017 Water82.0 82.0 81.8 81.8 81.8 TOTAL 100.0 100.0 100.0 100.0 100.0 log RLU4.02 4.12 4.14 4.35 5.15 Note: Sterile water control had log RLU of 7.39

What is claimed is:
 1. A method of disrupting a biofilm comprisingapplying to a surface having a biofilm an oral care compositioncomprising succinic acid, aconitic acid, and a carrier, said succinicacid and aconitic acid being present in the composition in a ratio ofsuccinic acid to aconitic acid of from about 0.9:1 to about 14:1 byweight.
 2. The method of claim 1 wherein said surface is a surface ofthe oral cavity.
 3. The method of claim 2 wherein said surface of theoral cavity is selected from the group consisting of surfaces of one ormore teeth, surfaces of the gums, and combinations of two or morethereof.
 4. The method of claim 3 wherein said composition has a ratioof succinic acid to aconitic acid of from about 0.9:1 to about 9:1. 5.The method of claim 3 wherein said composition has succinic acid andaconitic acid in a total combined amount of from about 0.1 to about 2%w/w of the composition.
 6. The method of claim 3 wherein saidcomposition has succinic acid and aconitic acid in a total combinedamount of from about 0.1 to about 1% w/w of the composition.
 7. Themethod of claim 3 wherein said composition has succinic acid andaconitic acid in a total combined amount of from about 0.1 to about 0.5%w/w of the composition.
 8. The method of claim 3 wherein saidcomposition has succinic acid and aconitic acid in a total combinedamount of from about 0.1 to about 0.3% w/w of the composition.
 9. Themethod of claim 3 wherein said composition is applied to the surface inthe form of a mouthwash or mouthrinse.
 10. The method of claim 3 whereinsaid composition is applied to the surface in the form of a toothpaste.11. The method of claim 3 wherein said applying step comprisescontacting the surface for less than thirty seconds.
 12. The method ofclaim 3 wherein said applying step comprises contacting the surface forthirty seconds or more.
 13. The method of claim 3 where said aconiticacid is trans-aconitic acid.
 14. The method of claim 3 wherein saidcarrier comprises a water/alcohol mixture.
 15. The method of claim 3wherein said composition comprises alcohol in an amount of about 10% v/vor less by volume of the total composition.
 16. The method of claim 3wherein said composition is free of alcohol.
 17. The method of claim 3wherein said method comprises removing biofilm from said surface. 18.The method of claim 3 wherein said method comprises reducing bacterialattachment to said surface.
 19. The method of claim 5 wherein saidaconitic acid is trans-aconitic acid.
 20. The method of claim 6 whereinsaid aconitic acid is trans-aconitic acid.